Diastereoselective alkylation of a chiral 1,4-benzodiazepine-2,5-dione containing the α-phenethyl group. Attempted asymmetric synthesis of α,β-diaminopropionic acid

Abstract

Alkylation of chiral benzodiazepinedione (S)-1 with LDA or LHMDS with N-(bromomethyl)- phthalimide (a protected derivative of bromomethylamine), via the lithium enolate of (S)-1 in the presence of HMPA as cosolvent was accomplished in moderate yield and good diastereo- selectivity. Hydrolysis of the resultant major diastereomeric product (S,R)-4 with 57% HI afforded the desired α,β-diaminopropionic acid 5 in good yield albeit in racemic form, probably due to β-elimination-addition of ammonia under these conditions.